title: DNMT1 and AIM1 Imprinting in human placenta revealed through a genome-wide screen for allele-specific DNA methylation.
abstract: BACKGROUND
  Genomic imprinting is an epigenetically regulated process wherein genes are expressed in a parent-of-origin specific manner. Many imprinted genes were initially identified in mice; some of these were subsequently shown not to be imprinted in humans. Such discrepancy reflects developmental, morphological and physiological differences between mouse and human tissues. This is particularly relevant for the placenta. Study of genomic imprinting thus needs to be carried out in a species and developmental stage-specific manner. We describe here a new strategy to study allele-specific DNA methylation in the human placenta for the discovery of novel imprinted genes.
  
  
  RESULTS
  Using this methodology, we confirmed 16 differentially methylated regions (DMRs) associated with known imprinted genes. We chose 28 genomic regions for further testing and identified two imprinted genes (DNMT1 and AIM1). Both genes showed maternal allele-specific methylation and paternal allele-specific transcription. Imprinted expression for AIM1 was conserved in the cynomolgus macaque placenta, but not in other macaque tissues or in the mouse.
  
  
  CONCLUSIONS
  Our study indicates that while there are many genomic regions with allele-specific methylation in tissues like the placenta, only a small sub-set of them are associated with allele-specific transcription, suggesting alternative functions for such genomic regions. Nonetheless, novel tissue-specific imprinted genes remain to be discovered in humans. Their identification may help us better understand embryonic and fetal development.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore. cmding@gmail.com.
authors.forename: Radhika
authors.initials: R
authors.lastname: Das
authors.forename: Yew Kok
authors.initials: YK
authors.lastname: Lee
authors.forename: Ruslan
authors.initials: R
authors.lastname: Strogantsev
authors.forename: Shengnan
authors.initials: S
authors.lastname: Jin
authors.forename: Yen Ching
authors.initials: YC
authors.lastname: Lim
authors.forename: Poh Yong
authors.initials: PY
authors.lastname: Ng
authors.forename: Xueqin Michelle
authors.initials: XM
authors.lastname: Lin
authors.forename: Keefe
authors.initials: K
authors.lastname: Chng
authors.forename: George Sh
authors.initials: GSh
authors.lastname: Yeo
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: Chunming
authors.initials: C
authors.lastname: Ding
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D018899:CpG Islands; D003459:Crystallins / Q000235:genetics*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D018392:Genomic Imprinting; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D017422:Sequence Analysis, DNA; D012727:Sex Characteristics; D013094:Spermatozoa / Q000378:metabolism
chemical_list: C105445:CRYBG1 protein, human; D003459:Crystallins; D008565:Membrane Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C000619381:Dnmt1 protein, mouse